TY - JOUR
T1 - Discovery of small alarmone synthetases and their inhibitors as toxin-antitoxin loci
JF - bioRxiv
DO - 10.1101/575399
SP - 575399
AU - Jimmy, Steffi
AU - Saha, Chayan Kumar
AU - Stavropoulos, Constantine
AU - Garcia-Pino, Abel
AU - Hauryliuk, Vasili
AU - Atkinson, Gemma C.
Y1 - 2019/01/01
UR - http://biorxiv.org/content/early/2019/04/11/575399.abstract
N2 - Under stressful conditions, bacterial RelA-SpoT Homologue (RSH) enzymes synthesise the alarmone (p)ppGpp, a nucleotide messenger. (p)ppGpp rewires bacterial transcription and metabolism to cope with stress, and at high concentrations inhibits the process of protein synthesis and bacterial growth to save and redirect resources until conditions improve. Single domain Small Alarmone Synthetases (SAS) are RSH family members that contain the (p)ppGpp synthesis (SYNTH) domain, but lack the hydrolysis (HD) domain and regulatory C-terminal domains of the long RSHs such as Rel, RelA and SpoT. We have discovered that multiple SAS subfamilies can be encoded in broadly distributed conserved bicistronic operon architectures in bacteria and bacteriophages that are reminiscent of those typically seen in toxin-antitoxin (TA) operons. We have validated five of these SASs as being toxic (toxSASs), and shown that the toxicity can be neutralised by six neighbouring antitoxin protein-coding genes. Thus, the ToxSAS-antiToxSAS system is a novel Type II TA paradigm comprising multiple different antitoxins, that exemplifies how ancient nucleotide-based signalling mechanisms can be repurposed as TA modules during evolution, potentially multiple times independently.
ER -